Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Advanced glycation endproducts (AGE) form as a result of non-enzymatic reaction of reducing sugars with proteins. Patients with chronic renal failure (CRF) have elevated AGE in plasma, skin and peritoneum. We measured AGE in the skin and peritoneum of individuals with CRF, patients undergoing continuous ambulatory peritoneal dialysis (CAPD) and in renal transplant recipients (TR). Pentosidine concentration and collagen-linked fluorescence (CLF) were measured. Pentosidine and CLF correlated in all patient groups (CRF r=0.688, p<0.01; CAPD r=0.674, p<0.05; TR r=0.811, p<0.01). Successful kidney transplant reduced AGE levels in the skin (CRF 11.7 +/- 4.51 U/mg; TR 5.02 +/- 3.13 U/mg, p<0.00001) and peritoneum (CRF 17.5 +/- 6.16 U/mg, TR 9.4 +/- 4.97 U/mg, p<0.0001). However in contrast to the TR group, CLF in peritoneum increased following CAPD (CRF 17.5 +/- 6.16 U/mg; CAPD 24.2 +/- 10.4 U/mg; p=0.06). Our results suggest that AGE might be formed in the peritoneum during CAPD treatment.
Cell Mol Biol (Noisy-le-grand) 1998 Nov
PMID:Effects of continuous ambulatory peritoneal dialysis and kidney transplantation on advanced glycation endproducts in the skin and peritoneum. 984 88

Advanced glycation endproducts (AGEs) accumulate in uraemia as a consequence of diminished clearance of low molecular weight forms which retain their reactivity and may subsequently combine with circulating and tissue macromolecules. Successful renal transplantation is the only form of renal replacement therapy which effectively clears these circulating AGEs; both haemodialysis and peritoneal dialysis are comparatively ineffective although high-flux haemodialysis confers some benefits. De novo AGE formation may be accelerated in uraemia due to carbonyl and oxidative stress leading to further accumulation. The consequences for the patient with chronic renal failure may be acceleration of vascular disease, renal failure progression and dialysis-related amyloidosis. Accelerated peritoneal AGE formation as a consequence of treatment with peritoneal dialysis fluids may be detrimental to peritoneal membrane function but does not appear to contribute to systemic elevation of AGEs.
Cell Mol Biol (Noisy-le-grand) 1998 Nov
PMID:The pathogenesis and consequences of AGE formation in uraemia and its treatment. 984 90

Selenium-dependent extracellular glutathione peroxidase (E-GPx) is found in plasma and other extracellular fluids. Previous studies have indicated that patients with chronic renal failure on dialysis have low plasma GPx activity. In this study, dialysis patients had approximately 40% of control plasma GPx activity, while anephric individuals had lowest plasma GPx activities ranging from 2 to 22% of control. The residual plasma GPx activity in anephric individuals could be completely precipitated by anti-E-GPx antibodies, indicating that all plasma GPx activity can be attributed to E-GPx in both normal and anephric individuals. Plasma GPx activity rises rapidly following kidney transplantation, often reaching normal values within 10 days. The plasma GPx activity in some transplanted patients rises to levels higher than the normal range, followed by a return to the normal range. Since E-GPx in the kidney is primarily synthesized in the proximal tubules, we investigated whether nephrotoxic agents known to disrupt proximal tubule function also affected plasma GPx activity. The beta-lactam antibiotic cephaloglycin rapidly caused a decrease in plasma GPx activity in rabbits. In addition, the chemotherapeutic agent ifosfamide caused a decrease in plasma GPx activity in pediatric osteosarcoma patients. Fanconi syndrome associated with either ifosfamide therapy or valproic acid therapy also caused a decrease in plasma GPx activity. Thus plasma GPx activity is related to kidney function and is decreased in certain situations where nephrotoxic drugs are administered. Monitoring plasma GPx activity may have predictive value in evaluating the function of transplanted kidneys or in predicting those patients particularly at risk of nephrotoxic injury associated with certain medications.
Mol Genet Metab 1998 Nov
PMID:Plasma glutathione peroxidase and its relationship to renal proximal tubule function. 985 89

The effects of oxalate on the metabolism of the isolated perfused rat liver were investigated. The main purpose was to verify if oxalate is also active in intact organs as demonstrated in isolated cells. The results revealed that the action of oxalate in the perfused liver resembles only partially that observed in isolated hepatocytes. In the perfused liver, oxalate inhibited gluconeogenesis from alanine, pyruvate and lactate, inhibited glycolysis and stimulated glycogenolysis. These observations confirm previous measurements with isolated hepatocytes. However, additional effects, not observed in isolated hepatocytes, were found. In the perfused liver, oxalate stimulated glucose production from dihydroxyacetone, glycerol or sorbitol. Moreover, the effects of oxalate in the perfused rat liver occurred at concentrations well above those reported for isolated hepatocytes, revealing that the compound is less toxic in the intact tissue. In vivo, the metabolic effects reported here can only be expected to occur at supra-physiological concentrations of oxalate, as in the case of a chronic renal failure.
Comp Biochem Physiol B Biochem Mol Biol 1998 Sep
PMID:Metabolic effects of oxalate in the perfused rat liver. 997 86

Biochemical modification of extracellular matrix (ECM) proteins can alter the function in overlying cells. We tested the hypothesis that metal-catalyzed oxidation of native ECM and individual matrix proteins modulates the activity of inducible nitric oxide synthase (iNOS) in cultured rat mesangial cells (RMC). Oxidized modification of native ECM resulted in a 32% increase in iNOS activity (P<0.01) without influencing the response to supplemental L-arginine or to the addition of the iNOS inhibitor, L-NAME. Immunoblot analysis indicated that enhanced iNOS activity was not associated with a parallel rise in the cytosolic content of iNOS. Synthesis of type IV collagen was unaffected by growth of RMC on oxidized native ECM. Oxidation of three normal constituents of the mesangial matrix - type IV collagen, laminin, and fibronectin - also stimulated iNOS activity in overlying RMC by 18-32% (P<0.05). Growth of RMC on oxidized type I collagen or Vitrogel had no effect on NO production. We conclude that oxidized modification of the mesangial matrix promotes increased iNOS activity and NO production by mesangial cells. Further work is required to determine whether this response limits glomerular injury or promotes damage to the mesangium in oxygen free radical-mediated diseases such as chronic renal failure, atherosclerosis and diabetes.
Int J Mol Med 1999 Mar
PMID:Growth of rat mesangial cells on oxidized extracellular matrix increases inducible nitric oxide synthase activity. 1002 60

The involvement of natriuretic peptides in the regulation of ACTH secretion in mice hemi-pituitary preparations was investigated. Atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP) and C-type natriuretic peptide (CNP) all inhibited CRF (10(-9) M)-evoked ACTH secretion over a concentration range of 10(-12)-10(-10) M and also stimulated cyclic GMP accumulation over a concentration range of 10 (-8)-10(-5) M. CNP was the most effective both in the inhibition of ACTH secretion and in the stimulation of cyclic GMP accumulation. Coincubation of hemi-pituitaries with 8bromo-cyclic GMP (10(-4) M) completely inhibited CRF (10(-9) M)-evoked ACTH secretion. Northern blot analysis revealed that all three major isoforms of the natriuretic peptide receptors are expressed in the mouse pituitary. These results demonstrate that natriuretic peptides do inhibit CRF-stimulated ACTH secretion from mouse pituitary preparations. A role for cGMP in mediating this effect on hormone secretion is indicated but the discrepancy between the efficacies of natriuretic peptides in inhibiting the secretory response and stimulating cyclic GMP accumulation suggest a more complicated stimulus-secretion coupling pathway is in operation.
Mol Cell Endocrinol 1999 Jun 25
PMID:Characterisation of the effects of natriuretic peptides upon ACTH secretion from the mouse pituitary. 1043 19

The expression of the endogenous CRF gene was examined in the human neuroblastoma cell line, BE(2)-M17. In this cell line, treatment with retinoic acid induces CRF mRNA transcription. We examined the requirement for the POU transcription factor, Bm-2, for this response. We confirmed that Bm-2 is expressed in retinoic acid-induced BE(2)-M17 cells. Expression of antisense Bm-2 message aborted the retinoic acid-mediated induction of CRF transcription. However, overexpression of Bm-2 was not sufficient for CRF expression in the absence of retinoic acid. These experiments support the hypothesis that Bm-2 is an intermediary for retinoic acid-induced CRF expression.
Mol Endocrinol 1999 Aug
PMID:A requirement for the POU transcription factor, Brn-2, in corticotropin-releasing hormone expression in a neuronal cell line. 1044

To purify novel ligands for the corticotrophin-releasing factor binding protein (CRF-BP) from ovine brain, whole brain was homogenised in methanol and the supernatant extracted on Sep-pak C18 cartridges followed by a preliminary HPLC step. Three peaks of ovine CRF-BP ligand activity were detected in the HPLC fractions, the first two of which were also detected by a specific corticotrophin-releasing factor two-site immunoradiometric assay, the third peak being detected by a human CRF-BP ligand assay, which will not detect ovine CRF. Human CRF-BP ligand-containing fractions were further purified by affinity chromatography on a human recombinant CRF-BP column with two additional HPLC steps. The human CRF-BP ligand was found to: (a) possess a molecular mass of 4707 Daltons, (b) have an N-terminal amino acid sequence (5 residues) identical to rat urocortin, (c) be detected by a specific urocortin radioimmunoassay, (d) have high affinity for both the human and ovine CRF-BPs and (e) be present in many regions of the ovine brain. Additionally, a 300 bp cDNA fragment sharing 83% homology with the rat urocortin gene was cloned from ovine brain, the product of which was predicted to have an identical amino acid sequence to that of rat urocortin. These pieces of information confirmed the identity of the human CRF-BP ligand as an ovine urocortin. The specially developed CRF-BP ligand assays showed that the rank orders of affinity of the CRF family members for human CRF-BP were: carp urotensin-1>>human CRF=rat/ovine urocortin>human urocortin>>frog sauvagine>>ovine CRF, and those for the ovine CRF-BP were: carp urotensin-1> human CRF=rat/ovine urocortin>human urocortin> frog sauvagine>>ovine CRF. This study describes a successful technique for the purification and detection of peptide ligands for the CRF-BP. We conclude that urocortin is the principal ligand for the CRF-BP in ovine brain and we could find no evidence for a centrally located mammalian sauvagine-like peptide.
J Mol Endocrinol 2000 Feb
PMID:Urocortin is the principal ligand for the corticotrophin-releasing factor binding protein in the ovine brain with no evidence for a sauvagine-like peptide. 1065 97

Chronic renal failure causes wide-ranging disturbances in male erectile function, and the dysfunction usually is not corrected by hemodialysis. In this study, erectile function and expression of nitric oxide synthase (NOS) isoforms, insulin-like growth factor-I (IGF-I), and IGF-I binding proteins were assessed in rats in which uremia had been produced by 5/6 nephrectomy. In the animals that suffered renal failure, there was a significantly lower rise in intracavernosal pressure in response to electrical stimulation, and the mean patency period after cavernous nerve stimulation was significantly increased. The amount of neuronial NOS mRNA was significantly higher in the penile tissues and major pelvic ganglia (MPG) of uremic rats than in control animals. There consistently were higher levels of nNOS and endothelial NOS in the penile tissues and MPG of rats with renal failure, and there was a significant decrease in the amount of IGF-I gene expression in the MPG of these animals. Expression of the IGF binding proteins 2 and 4 but not 5 also was reduced. This preliminary work demonstrates that impairment of erection in chronic renal failure in the rat is attributable to a disturbance in NOS gene expression with concomitant changes in IGF-I. These discoveries may permit an improved therapeutic approach to men with erectile dysfunction associated with chronic renal failure.
Mol Urol 1999
PMID:Experimental Chronic Renal Failure-Associated Erectile Dysfunction: Molecular Alterations in Nitric Oxide Synthase Pathway and IGF-I System. 1085 13

Prenatal exposure to ethanol (E) enhances the offspring's ACTH and corticosterone responses to stressors. Here, we determined the role of increased pituitary responsiveness and/or PVN neuronal activity in this phenomenon. Pregnant rats were exposed to E vapors during days 7-18 of gestation, and we compared the responses of their 55- to 60-day-old offspring (E rats) to those of control (C) dams. PVN mRNA levels of the immediate early genes (IEGs) c-fos and NGFI-B, which were low under basal conditions in all groups, showed a peak response 15 min after shocks and 45 min after LPS treatment. These responses were significantly enhanced in E, compared to C offspring of both genders. CRF, but not VP hnRNA levels were also significantly higher in the PVN of shocked E offspring. Resting median eminence content of CRF and VP, and pituitary responsiveness to CRF, were unchanged, while responsiveness to VP was marginally increased in females. These results indicate that prenatal alcohol selectively augments the neuronal activity of hypothalamic CRF perikarya.
Mol Cell Neurosci 2000 Oct
PMID:Increased activity of the hypothalamic-pituitary-adrenal axis of rats exposed to alcohol in utero: role of altered pituitary and hypothalamic function. 1108 85


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